Betalutin (177Lu-lilotomab satetraxetan) / Thor Medical - LARVOL DELTA

Radioimmunotherapy of Non-Hodgkin Lymphoma with Lilotomab Conjugated to Different Radionuclides: A Simulation Study (EANM 2025) - "[Lu-177]Lu-lilotomab satetraxetan targets the CD37 antigen on B-cells and was investigated for relapsed indolent non-Hodgkin lymphoma patients in the phase 1/2a trial LYMRIT-37-01...Further work will focus on including information from early time points in the RM calculations and estimating absorbed doses to tumors to compare the therapeutic efficacy. This may contribute to inform the design of a new lilotomab-based radioimmunotherapy."

Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

Comprehensive analysis of 177Lu-lilotomab satetraxetan in lymphoma cell lines: Implications for precision radioimmunotherapy and combination schemes. (PubMed, Br J Haematol) - "177Lu-lilotomab satetraxetan (Betalutin) is an anti-CD37 radioimmunoconjugate evaluated as a single administration therapy for the treatment of patients with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL)...However, BCL2 expression was higher in resistant than in sensitive GCB-DLBCL cell lines, and the addition of the BCL2 inhibitor venetoclax showed synergism when added to the radioimmunoconjugate. Finally, the pattern of activity of 177Lu-lilotomab satetraxetan differed from what was achieved with a CD37-targeting antibody-drug conjugate or with Rituximab cyclophosphamide hydroxydaunorubicin (doxorubicin) oncovin prednisone (R-CHOP), indicating the potential benefit of the beta-emitter payload. This systematic analysis of the responsiveness of lymphoma cell lines to CD37-targeting radioimmunotherapy consolidated 177Lu-lilotomab satetraxetan as a promising compound for the treatment of CD37-positive malignancies and identified candidate..."

IO biomarker • Journal • Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • MYC

Impact of Total Tumour Absorbed Dose and Total Metabolic Tumour Volume on Progression Free Survival in the Phase 1/2a Study of [177Lu]Lu-Lilotomab Satetraxetan for Treatment of Relapsed Indolent Non-Hodgkin Lymphoma (EANM 2024) - "While a survival benefit was indicated for patients receiving tumour absorbed doses over 200 cGy, the difference was not significant, and further work will focus on establishing a larger data foundation. tMTVbaseline did not predict PFS, which was not surprising since different treatment regimens were explored. However, a significant difference in PFS was found when separating the population based on tMTV3months median, implicating that this parameter may have a prognostic value for patients treated with [177Lu]Lu-lilotomab satetraxetan."

P1/2 data • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PARADIGME: A Phase 1/2 Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=191 | Completed | Sponsor: Nordic Nanovector | Active, not recruiting ➔ Completed

Trial completion • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

LYMRIT-37-07: Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Nordic Nanovector | Phase classification: P1b ➔ P1

Combination therapy • Phase classification • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector Publishes Data from the PARADIGME Phase 2 Clinical Trials with Betalutin on European Clinical Trials Database (PRNewswire) - P1b/2a | N=191 | LYMRIT-37-01 (NCT01796171) | Sponsor: Nordic Nanovector | "Nordic Nanovector ASA...announces that full results from its Phase 2 clinical trials of Betalutin^® (177 Lu lilotomab satetraxetan) in resistant/refractory (R/R) indolent non-Hodgkin's lymphoma (NHL) have been published at EudraCT, the European Union Drug Regulating Authorities Clinical Trials Database...The data from the 109 patients enrolled in PARADIGME up until its discontinuation show: Overall response rate (ORR) was 38.9% and 32.1%; complete response (CR) rate was 20.8% and 14.3% in participants receiving doses of 40/15 (Betalutin^® dose of 15 MBq/kg after a pre-dose of 40 mg lilotomab) and 100/20 (Betalutin^® dose of 20 MBq/kg after a pre-dose of 100 mg lilotomab), respectively."

P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

B-Cell Targeting Anti-CD37 Humanized Antibodies Engineered for Potent Effector Functions and Extended Plasma Half-Life (ASH 2022) - "Of note, the anti-CD37 antibody-drug conjugates (ADC) naratuximab emtansine and the CD37-targeting radioimmunotherapy (RIT) Betalutin have shown efficacy in NHL patients during clinical testing... The humanized anti-CD37 candidates were characterized in vitro and in vivo and benchmarked against the anti-CD20 antibodies approved for NHL treatment, rituximab and obinutuzumab, and a recombinant version of the bi-paratopic anti-CD37 antibody DuoHexaBody-CD37, currently in Phase I clinical development... Taken together, the humanized and Fc-engineered anti-CD37 antibodies show potent effector functions, favorable pharmacokinetic properties and in vivo therapeutic efficacy. As such, the designed CD37 antibodies should be attractive modalities in targeted treatment of B cell malignancies, such as NHL, including lymphomas non-responding to anti-CD20 treatments, but also potentially for B-cell driven autoimmune disorders."

IO biomarker • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

BETALUTIN® IN PATIENTS WITH RELAPSED/ REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) NOT ELIGIBLE FOR AUTOLOGOUS STEM CELL TRANSPLANT (EHA 2022) - "Aims This was an open label Phase I, multi‑centre, single ascending dose study of four different treatment regimens of Betalutin® administered after rituximab pre-treatment and lilotomab pre‑dosing. Conclusion Betalutin® is well tolerated in relapsed/ refractory DLBCL and a MTD was not reached in this study. The initial efficacy and safety findings from this study warrant further investigation of Betalutin® as a single agent or in combination with a standard of care treatment in relapsed/refractory DLBCL."

Clinical • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Nordic Nanovector and APIM Therapeutics Announce Merger Agreement (Market Screener) - "Nordic Nanovector ASA...announce that they have entered into a definitive merger agreement to combine the companies in an all-stock transaction (the 'Agreement'). Subject to completion of the Agreement, Nordic Nanovector will purchase shares in APIM, and become the parent entity of APIM (the 'Transaction'). The Agreement follows the review that Nordic Nanovector conducted, in conjunction with Carnegie Investment Bank, to optimise shareholder value following its decision to discontinue the PARADIGME study for Nordic Nanovector's lead asset Betalutin....The Transaction is structured as an acquisition of shares in APIM by Nordic Nanovector, with an equity valuation of APIM at NOK 439 million plus any net cash raised prior to completion of the Transaction. Through the exercise of existing warrants held by current APIM shareholders, a minimum of NOK 55 million is contemplated to be raised prior to completion of the Transaction."

M&A • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

LYMRIT-37-07: Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL (clinicaltrials.gov) - P1b | N=7 | Completed | Sponsor: Nordic Nanovector | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Aug 2022

Combination therapy • Trial completion • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PARADIGME: A Phase I/II Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=191 | Active, not recruiting | Sponsor: Nordic Nanovector | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ Nov 2022 | Trial primary completion date: Sep 2021 ➔ Nov 2022

Enrollment closed • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector to Discontinue PARADIGME, its Phase 2b Trial with Betalutin in 3L R and R Follicular Lymphoma (PRNewswire) - "Nordic Nanovector ASA...provides an update on PARADIGME, its Phase 2b trial of Betalutin (177Lu lilotomab satetraxetan) in 3rd-line relapsed and anti-CD20 refractory follicular lymphoma (3L R and R FL). Following a comprehensive review and independent data evaluation of PARADIGME and a subsequent request for regulatory agency interaction, the Board of Directors (Board) has taken the difficult decision to discontinue the study. No further patients will be enrolled into PARADIGME. The PARADIGME trial enrolled a total of 109 patients....The Company will therefore explore potential partnerships and will also seek advice from the US Food and Drug Administration (FDA) to discuss if there could be a possible way forward for Betalutin in an alternative setting."

FDA event • Licensing / partnership • Trial suspension • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector to Seek Regulatory Feedback Following its Preliminary Review and Independent Data Evaluation of PARADIGME, its Phase 2b Trial with Betalutin in R/R Follicular Lymphoma (PRNewswire) - P1/2 | N=204 | PARADIGME (NCT01796171) | Sponsor: Nordic Nanovector | "The independent expert panel reviewed the efficacy data collected to date. Betalutin®, at the selected dose of 15 MBq/kg after a pre-dose of 40 mg lilotomab (40/15), has continued to display an attractive safety profile. While Betalutin® showed signs of efficacy in this frail, elderly and difficult-to-treat patient population, the independent expert panel reported that the efficacy data are less promising than the data reported from the Phase 2a LYMRIT 37-01 trial. The Company intends to seek further guidance from the competent regulatory authorities, including the US Food and Drug Administration (FDA), regarding the way forward for PARADIGME....Given the continuing slow patient recruitment, Nordic Nanovector does now not expect to deliver preliminary top line data from PARADIGME in H2 2022."

DSMB • P2b data • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector Announces that the data from the LYMRIT 37-05 Phase 1 Trial of Betalutin in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) will be presented at EHA 2022 Meeting (PRNewswire) - P1 | N=18 | LYMRIT-37-05 (NCT02658968) | Sponsor: Nordic Nanovector | "Nordic Nanovector ASA...announces an update from the LYMRIT 37-05 Phase 1 trial investigating Betalutin® (177Lu lilotomab satetraxetan) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for stem cell transplantation. The latest data to be presented at the European Hematology Association (EHA) Congress in Vienna, Austria on 10 June 2022 shows that Betalutin® continues to be well tolerated with no further dose-limiting toxicity (DLT). The data analysis showed that clinical activity of Betalutin® was seen with two complete responses out of 16 evaluable patients."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector to Conduct a Comprehensive Review and Independent Data Evaluation of PARADIGME, its Phase 2b Trial with Betalutin in R/R FL as a Result of Continuing Slow Recruitment (PRNewswire) - "Nordic Nanovector ASA...provides an update on PARADIGME, its ongoing Phase 2b trial of Betalutin® (177Lu lilotomab satetraxetan) in 3rd-line relapsed rituximab/anti-CD20 refractory follicular lymphoma (3L R/R FL)....Despite ongoing efforts by the company this has continued into Q2 with no additional patients enrolled in May....As a result, the Board of Nordic Nanovector has decided to conduct a comprehensive review of all aspects of the PARADIGME study....PARADIGME will continue to enrol patients while the independent evaluation is ongoing. The current guidance for delivery of initial top line data from PARADIGME in the second half of this year will be reviewed concurrently. The Board expects to report on the findings of the review of PARADIGME no later than the Q2 results to be released on 20 July 2022 and will not be commenting further until the review is complete."

P2b data • Trial status • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

FDG PET/CT and Dosimetric Studies of Lu-Lilotomab Satetraxetan in a First-in-Human Trial for Relapsed Indolent non-Hodgkin Lymphoma-Are We Hitting the Target? (PubMed, Mol Imaging Biol) - "tTAD of ≥ 200 cGy may prove valuable to ensure clinical response, but further studies are needed to confirm this in a larger patient population. Furthermore, this work indicates that higher baseline tumor burden (up to 585 cm) did not induce reduction in radioimmunoconjugate accumulation in tumor."

FDG PET • Journal • P1 data • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

LYMRIT-37-07: Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL (clinicaltrials.gov) - P1b | N=7 | Active, not recruiting | Sponsor: Nordic Nanovector | Trial completion date: Jun 2025 ➔ Dec 2022

Combination therapy • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector Provides update on PARADIGME, its Phase 2b Pivotal Trial with Betalutin in R/R Follicular Lymphoma (PRNewswire) - "Nordic Nanovector ASA...provides an update on the timeline for PARADIGME, its ongoing pivotal Phase 2b trial of Betalutin® (177Lu lilotomab satetraxetan) in 3rd-line relapsed rituximab/anti-CD20 refractory follicular lymphoma (3L R/R FL). The Company reports that 106 patients have been enrolled into PARADIGME as of 6 January 2022....The Company now anticipates the preliminary three-month data readout from PARADIGME to be reported during the second half of 2022 (previously first half of 2022)."

Enrollment status • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Nordic Nanovector R&D Day: Building Value from Betalutin® and a pipeline of broader therapeutic opportunities targeting CD37 https://t.co/SAbn4e5jtz" (@CisionNews)

LYMRIT-37-07: Study of Safety and Efficacy of Betalutin and Rituximab in Patients With FL (clinicaltrials.gov) - P1b; N=7; Active, not recruiting; Sponsor: Nordic Nanovector; Recruiting ➔ Active, not recruiting; N=25 ➔ 7; Trial primary completion date: Sep 2020 ➔ Nov 2022

Clinical • Combination therapy • Enrollment change • Enrollment closed • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MRI

LYMRIT 37-01: A Phase I/II Study of 177lu-Lilotomab Satetraxetan (Betalutin®) Antibody-Radionuclide-Conjugate (ARC) for the Treatment of Relapsed Non-Hodgkin's Lymphoma (NHL) - Analysis with 6-Month Follow-up (ASH 2018) - "...In addition, many pts eventually develop resistance to rituximab (RTX)/RTX-containing regimens, thus therapeutic targets other than CD20 are important...One case of CMML occurred 24 m after Betalutin (18 m after subsequent bendamustine-RTX therapy)...With a single administration, Betalutin has the potential to be a novel, safe, and effective therapy for pts with B-cell malignancies. The 2 RP2Ds from Part A of the study are now being compared in a randomized phase 2b cohort (Part B: “PARADIGME”) in relapsed, RTX/anti-CD20 refractory FL pts who have received ≥2 prior therapies."

P1/2 data • Biosimilar • Cardiovascular • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Indolent Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Study of Betalutin for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma (LYMRIT-37-05) (clinicaltrials.gov) - P1; N=18; Completed; Sponsor: Nordic Nanovector; Recruiting ➔ Completed; Trial completion date: Dec 2022 ➔ Jul 2021

Clinical • Trial completion • Trial completion date • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Myelosuppression in patients treated with Lutetium-lilotomab satetraxetan can be predicted with absorbed dose to the red marrow as the only variable. (PubMed, Acta Oncol) - "The sigmoid function gave similar results in terms of accuracy when compared to the linear model. Myelosuppression in the form of thrombocytopenia and neutropenia in patients treated with [Lu]Lu-lilotomab satetraxetan can be predicted from the SPECT/CT-derived absorbed dose estimate to the red marrow."

Clinical • Journal • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

Nordic Nanovector Provides Update on PARADIGME, its Phase 2b Pivotal Trial with Betalutin in R/R Follicular Lymphoma (PRNewswire) - "Nordic Nanovector...provides an update on the timeline for PARADIGME, its ongoing pivotal Phase 2b trial of Betalutin® (177Lu lilotomab satetraxetan) in 3rd-line relapsed rituximab/anti-CD20 refractory follicular lymphoma (3L R/R FL). The Company, having reviewed the recent rate of patient recruitment in discussion with its clinical advisors and in light of the continuing impact from the COVID pandemic, now anticipates the preliminary three-month data readout from PARADIGME during the first half of 2022...The Company reports that 92 patients have been enrolled into PARADIGME as of 3 August, compared with 83 patients enrolled as of 25 May 2021 and 73 as of 17 February 2021...the rate of patient recruitment has been slower than anticipated."

Enrollment status • P2 data • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Nordic Nanovector Announces Initial Results from LYMRIT 37-05 Phase 1 Trial of Betalutin® in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) (PRNewswire) - P1, N=18; NCT02658968; Sponsor: Nordic Nanovector; "Nordic Nanovector...announces encouraging initial results from the LYMRIT 37-05 Phase 1 trial investigating Betalutin® (177Lu lilotomab satetraxetan) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for stem cell transplantation....The initial results from the completed Phase I study (n=16 treated with Betalutin®) show that Betalutin® was well tolerated, with a good safety profile consistent with all previous studies with Betalutin...Our near-term focus remains very much on completing PARADIGME in 3rd-line follicular lymphoma and delivering top line 3-month data by the end of 2021."

P1 data • P2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology